Oligonucleotide (ON) chelate complexes are two or more ONs linked intermolecularly by a divalent or other multivalent metal cation. ON chelate complexes neutralize the inherent chelation properties of ONs which can contribute to administration-related side effects with these compounds. The administration of ON chelate complexes is a novel method of administering an ON to a subject where administration-related side effects associated with un-chelated ONs are mitigated. These side effects may include shivering, fever and chills with intravenous infusion or induration, inflammation and pain at the injection site with subcutaneous administration. Moreover, by preparing ONs as chelated complexes, their pharmacokinetic behavior may be improved, providing for increased therapeutic performance with similar dosing compared to unchelated ONs. The characterization and properties of ON chelate complexes were previously described in International application publication no. WO 2012/021985 and U.S. application publication no. 2012/0046348, which are incorporated herein by reference in their entirety.
ON chelate complexes provide for an improved method of administering ONs with reduced side effects without affecting the biochemical activity of the ON when administered as a simple sodium salt.
ON chelate complexes comprising an ON which acts by a sequence dependent or sequence independent mechanism can have a therapeutic effect in a disease state which may not provide for an optimal therapeutic result in the diseased subject undergoing treatment with the ON chelate complex.
Accordingly, there is a need in the art to provide for an improved novel composition which comprises an ON chelate complex such as in a combination formulation.
Antiviral ON chelate complexes comprising an antiviral ON which acts by sequence dependent or sequence independent mechanisms can have an antiviral effect against different viral infections. These antiviral effects may not provide for an optimal therapeutic result in the subject with an existing viral infection undergoing treatment with the ON chelate. A further improved therapeutic result may be achieved by the simultaneous use of an antiviral ON chelate complex and a polypeptide-based immunotherapy with known antiviral activity.
Accordingly, there is a need in the art to provide for a novel composition which comprises an antiviral ON chelate complex and an antiviral polypeptide or pegylated polypeptide in combination. Ideally the antiviral polypeptide would also have activity against the viral infection in question, either by affecting the same target/biochemical pathway as the antiviral ON chelate in question or by affecting a target/biochemical pathway distinct from that affected by the antiviral ON chelate complex.